title: A single dose of intravenous zoledronate prevents glucocorticoid therapy-associated bone loss in acute flare of Crohn's disease, a randomized controlled trial.
abstract: OBJECTIVE
  To assess the effectiveness and safety of zoledronate (ZOL) in preventing glucocorticoid therapy-associated bone loss in patients with acute flare of Crohn's disease (CD) in a randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Forty CD patients starting a glucocorticoid therapy (60 mg prednisolone per day) for acute flare (CD activity index (CDAI) >220) were randomized to compare the effect of ZOL (4 mg intravenous, n=20) or placebo (n=20) on change in lumbar bone mineral density (BMD). All patients received calcium citrate (800 mg) and colecalciferol (1,000 IU) daily. Dual energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4) was performed at baseline and day 90. Follow-up examinations at day 1/7/14/30 and 90 included laboratory tests and adverse event/serious adverse events reports.
  
  
  RESULTS
  Thirty-six patients were available for per-protocol analysis. With placebo (n=18), a decrease in BMD was seen (T-score: -0.98 ± 0.8, day 0 and -1.25 ± 0.77, day 90, P=0.06), with ZOL (n=18) BMD increased (-1.15 ± 1.02, day 0 and -0.74 ± 1.09, day 90, P=0.03). The change in BMD under placebo (-0.26 ± 0.21) vs. ZOL (+0.41 ± 0.19) was highly significant (P=0.006). In all, 14 out of 18 patients with ZOL had an increase in BMD (+0.64 ± 0.48), 12 of 18 with placebo a decrease (-0.50 ± 0.39). Changes of clinical findings and laboratory results of inflammation (leukocytes, platelets, and C-reactive protein) were the same in- and between-groups throughout the study. With ZOL, serum bone degradation marker β-Cross-Laps decreased. Study medication was safe and well tolerated.
  
  
  CONCLUSIONS
  ZOL is effective in preventing glucocorticoid therapy-induced bone loss in patients with acute flare of CD and should be considered whenever a glucocorticoid therapy is started in CD patients.
authors.affiliation: Department of Internal Medicine I, University of Ulm, Ulm, Germany. jochen.klaus@uniklinik-ulm.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Klaus
authors.forename: M M
authors.initials: MM
authors.lastname: Haenle
authors.forename: C
authors.initials: C
authors.lastname: Schröter
authors.forename: G
authors.initials: G
authors.lastname: Adler
authors.forename: G
authors.initials: G
authors.lastname: von Boyen
authors.forename: M
authors.initials: M
authors.lastname: Reinshagen
authors.forename: C
authors.initials: C
authors.lastname: von Tirpitz
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000517:prevention & control*; D003424:Crohn Disease / Q000188:drug therapy* / Q000503:physiopathology; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids; D007093:Imidazoles; D000077211:Zoledronic Acid